Volume 33, Issue 159 (July & August 2025)                   J Adv Med Biomed Res 2025, 33(159): 340-346 | Back to browse issues page

Ethics code: IR.ZUMS.REC.1402.066

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Abyar A, Mohammadzadeh A, Dehghanzad R, Keramatipour M. A Canonical Splice Site Variant in the Last Intron of the COL4A5 Gene Causing X-Linked Alport Syndrome in an Iranian Family: A Case Report. J Adv Med Biomed Res 2025; 33 (159) :340-346
URL: http://journal.zums.ac.ir/article-1-7645-en.html
A Canonical Splice Site Variant in the Last Intron of the COL4A5 Gene Causing X-Linked Alport Syndrome in an Iranian Family: A Case Report
Amirhossein Abyar1 , Akbar Mohammadzadeh1 , Reyhaneh Dehghanzad2 , Mohammad Keramatipour *3
1- Department of Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
2- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
3- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran & Watson Genetic Laboratory, North Kargar Street, Tehran, Iran , m@keramati.org
Abstract:   (162 Views)

Alport syndrome (AS) is an inherited disorder of collagen type IV causing progressive renal disease, sensorineural hearing loss, and ocular abnormalities with variable severity. Here, we report a splice site variant in the COL4A5 gene, leading to X-linked Alport syndrome (XLAS) in two siblings from a non-consanguineous Iranian family. The proband was a 10-year-old boy with hematuria, proteinuria, and mild to moderate bilateral sensorineural hearing loss (BSNHL), who was diagnosed with AS based on renal pathology and genetic testing. Whole exome sequencing of the proband identified a hemizygous canonical splice site variant (c.4994+1G>A) in intron 52 of the COL4A5 gene. The same mutation was detected in his affected brother and heterozygous mother by Sanger sequencing, confirming the diagnosis of XLAS in the two affected individuals with renal impairment in this family. Our findings expand the geographic and mutational spectrum of COL4A5 splice site variants. To the best of our knowledge, this is the first reported c.4994+1G>A variant (ClinVar: rs2524654509) in an Iranian family, underscoring the need for including splice site analysis in diagnostic testing.

Keywords: Alport Syndrome, COL4A5 Protein, Human, RNA Splice Sites, Collagen Type IV, Exome Sequencing
     
Type of Study: Case Report Article | Subject: Clinical Medicine
Received: 2025/04/14 | Accepted: 2025/09/5 | Published: 2025/09/29
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